ETHNOMEDICAL RELEVANCE: The anti-inflammatory activity of both systemic and local administrations of essential oil from nigella sativa L. has been shown.AIM OF THE STUDY: Therefore, the effect of nigella sativa on tracheal responsiveness (TR) and lung inflammation of sulfur mustard (SM) exposed guinea pigs was examined. MATERIALS AND METHODS: Guinea pigs were exposed to diluent solution (control group), inhaled SM (SME group), SME treated with nigella sativa (SME+N), SME treated with dexamethasone (SME+D) and SME treated with both drugs (SME+N+D), (n=7 for each group). TR to methacholine, total white blood cell (WBC) and differential WBC count of lung lavage, and serum cytokines were measured 14 days post-exposure. RESULTS: The values of TR, eosinophil, monocyte, lymphocyte, interleukine-4 (IL-4) and interferon gamma (IFN-?) of SME group were significantly higher than those of controls (p<0.05 to p<0.001). The TR in SME+N, SME+D and SME+N+D was significantly lower compared to that of SME group (p<0.01 for all cases). The percentage of eosinophil in SME+D, and the percentage of monocyte in SME+N+D (p<0.05 to p<0.01) were significantly lower than those in SME group. The neutrophil number was decreased in SME+N and SME+N+D groups compared to SME animals (p<0.05 to p<0.01). IL-4 levels in serum of SME+N (p<0.01), SME+D (p<0.05), SME+N+D (p<0.01) and IFN-? in SME+N (p<0.05) were greater than those in SME animals. CONCLUSIONS: These results showed a preventive effect of nigella sativa on TR and lung inflammation of SM exposed guinea pigs.